Agmatine blocks
morphine withdrawal symptoms and enhances
morphine analgesia in rats. Yet, the role of
agmatine in the pharmacological effects of other abused drugs has not been investigated. The present study investigates the effect of
agmatine administration on the hypothermic response to
cannabinoids.
Hypothermia is an effective endpoint because
cannabinoid agonists produce a rapid, reproducible, and significant decrease in body temperature that is abolished by
cannabinoid CB(1) receptor antagonists.
WIN 55212-2, a
cannabinoid agonist, was administered to rats by itself and with
agmatine.
WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.) caused a significant
hypothermia.
Agmatine (10, 25 and 50 mg/kg, i.p.) was ineffective. For combined administration,
agmatine (50 mg/kg, i.p.) enhanced the hypothermic effect of
WIN 55212-2 (1, 2.5, 5 and 10 mg/kg, i.m.). The enhancement was strongly synergistic, indicated by a 2.7-fold increase in the relative potency of
WIN 55212-2. The central administration of
agmatine (25 and 50 mug/rat, i.c.v.) significantly increased the hypothermic effect of
WIN 55212-2 (2.5 mg/kg, i.m.). This indicates that
agmatine acts through a central mechanism to augment
cannabinoid-evoked
hypothermia.
Idazoxan (2 mg/kg, i.p.), an
imidazoline antagonist, blocked the enhancement by
agmatine, thus suggesting that
imidazoline receptor activation is required for
agmatine to enhance
cannabinoid-evoked
hypothermia. The present data reveal that
agmatine and a
cannabinoid agonist interact to produce a hypothermic synergy in rats. These results show that
agmatine acts in the brain and via
imidazoline receptors to enhance
cannabinoid-evoked
hypothermia.